Mitral valve surgery, including mitral valve repair, can alleviate the state of volume overload in the left ventricle (LV) caused by mitral regurgitation (MR) and initiate the process of reverse remodeling. Various studies have demonstrated that mitral valve surgery significantly reduces LV volumes and dimensions, effects which persist over time. The left ventricular end-diastolic volume (LVEDV), primarily influenced by preload, tends to decrease more than the end-systolic volume (LVESV), which is more affected by afterload. Generally, these changes result in an initial decrease in ejection fraction (EF) post-surgery. However, as time progresses following MR surgical correction, LV reverse remodeling may occur, manifesting as an increase in EF after the initial decrease. Nonetheless, several questions remain regarding reverse remodeling after mitral valve repair. Most available data are derived from observational studies, which are prone to various biases, such as analyzing only patients with successful mitral repairs or those with good long-term survival rates.

The CardioLink-2 trial of the Canadian Mitral Research Alliance (CAMRA) examined resection-based mitral repair techniques (primarily quadrangular resection) versus posterior leaflet preservation (neochord implantation) as mitral repair options for patients with posterior leaflet prolapse. At 12 months postoperatively, no significant differences were found in the effect on mean mitral gradient at peak exercise. The objective of this sub-analysis of the same trial was to evaluate the impact of both mitral repair techniques on LV reverse remodeling after one year of follow-up.

A total of 104 patients were randomly assigned to either a leaflet resection or preservation strategy. Blinded echocardiograms were analyzed preoperatively, prior to discharge, and at 12 months postoperatively in an independent central imaging lab. All patients underwent successful mitral repair. At discharge, 3 patients presented with moderate MR, while the remainder had mild or lesser degrees of MR. Compared to baseline, indexed LVEDV was significantly reduced at the discharge echocardiogram (p < 0.0001) and further decreased at the 12-month echocardiogram (p = 0.01). In contrast, indexed LVESV did not change significantly from baseline in the predischarge echocardiogram (p = 0.32) but improved significantly at 12 months postoperatively (p < 0.0001), resulting in a corresponding improvement in EF at 12 months (p < 0.0001).

The authors concluded that the type of mitral repair technique used did not affect LV reverse remodeling after surgery, which occurred in distinct phases. Although LVEDV improvement was noted pre-discharge, significant improvement in LVESV was observed one year postoperatively.

COMMENTARY:

Recently, in a retrospective study reviewed on this blog, Wijngaarden et al. demonstrated the equivalency of both mitral repair techniques in preserving postoperative LV function in cases of degenerative MR. Today’s featured article by Hibino et al. is a post-hoc analysis of the CAMRA CardioLink–2 trial, which again shows LV function preservation following different mitral repair techniques. In this study, early LV reverse remodeling was documented in predischarge echocardiograms and was especially notable at 12 months, with progressive improvement in indexed LVEDV reduction. However, indexed LVESV showed no significant change in predischarge measurements but decreased at the 12-month follow-up. Consequently, EF dropped sharply by 10 points (preoperative 61.1% vs. predischarge 51.7%; p < 0.0001). Although there was significant improvement in indexed LVESV and EF at 12 months (56.4%; p < 0.0001), EF never returned to preoperative levels. This early decrease in EF, with only partial recovery over a year, has been previously observed in other studies and likely reflects the prolonged delay in surgical intervention in these patients. Asymptomatic or minimally symptomatic patients are often managed with a “watchful waiting” strategy until symptoms become more evident, significant pulmonary hypertension develops, atrial fibrillation occurs, or LV dimensions and/or EF worsen before surgery is considered. However, irreversible LV function changes may occur in a significant proportion of these patients before the criteria indicating surgery are detected. In such cases, although mitral repair is performed, these irreversible changes may influence long-term prognosis and survival.

This study also revealed other relevant findings, including an early and sustained reduction in pulmonary pressures and indexed left atrial volume. In contrast, no changes were observed in tricuspid regurgitation over time (only 4 patients in the study underwent tricuspid annuloplasty). As shown in the retrospective study by Wijngaarden et al., both leaflet resection and chord replacement are effective mitral repair techniques in preserving LV function post-surgery. Additionally, this latest study incorporated the novel measurement of global longitudinal strain (GLS) as a more sensitive and less volume-dependent echocardiographic parameter for assessing LV function.

Hibino et al.’s study, although with some limitations worth noting, does not appear heavily biased. The reported results are based on an intention-to-treat analysis, whereas most previous studies focus exclusively on actual treatment received, which may be more useful for predicting retrospective outcomes. Furthermore, the series analyzed comprises a homogeneous and well-compensated population, as all patients presented posterior leaflet prolapse and EF over 40%, which is usually the case for patients undergoing mitral repair in clinical practice. However, it is unclear whether these results can be applied to patients with more impaired EF or other MR etiologies. We should also consider that echocardiographic follow-up was limited to a maximum of 1 year, which may be considered a relatively short period. Indeed, retrospective studies have demonstrated full EF recovery at 2 years in patients with baseline EF below 50%. A future sub-analysis of this study may confirm these findings. In contrast, it is important to highlight the study’s significant strengths, as it is prospective, randomized, and features high-quality echocardiographic follow-up, independent and far more rigorous than most published retrospective series to date.

Current guidelines establish that an EF of 60% or an LVESD of 4 cm are the thresholds indicating the need for repair. These criteria were designed based on studies that defined mitral repair success as achieving an EF of at least 50% in 75% of patients at 1 and 12 months post-repair. Hibino et al.’s study also supports the idea that a 1-year EF assessment is the appropriate measure for evaluating mitral repair outcomes. Therefore, these findings align with current recommended surgical criteria. The question that remains unanswered is whether we should be less permissive with current repair thresholds to avoid irreversible changes and improve prognosis in these patients.

The true value of this study lies in its high quality as a randomized clinical trial and its prospective echocardiographic findings, which demonstrate that a full year, rather than just 30 days, is required to assess the real and complete effectiveness of mitral repair. In any case, the practical takeaway from this article is that both surgical repair techniques perform well regarding LV recovery. Therefore, it is crucial to select the mitral repair technique that provides confidence and comfort, but more importantly, to ensure no residual MR greater than mild remains at the end of surgery. This is the only guarantee of sustained reverse remodeling over time.

REFERENCE:

Hibino M, Dhingra NK, Verma S, Chan V, Quan A, et al.; CAMRA Trial CardioLink-2 Collaborators. Mitral repair with leaflet preservation versus leaflet resection and ventricular reverse remodeling from a randomized trial. J Thorac Cardiovasc Surg. 2023 Jul;166(1):74-83.e2. doi: 10.1016/j.jtcvs.2021.08.081.